RELAXATION AND INHIBITION OF CONTRACTILE RESPONSE TO ELECTRICAL-FIELDSTIMULATION BY BERAPROST SODIUM IN CANINE AIRWAY SMOOTH-MUSCLE

To elucidate the effect of Beraprost, a stable prostaglandin (PG) I2 a nalogue, on airway smooth muscle functions and its mechanism of action , we studied canine bronchial segments under isometric conditions in v itro. Addition of PGI2 and its analogues dose-dependently relaxed bron chial smooth muscle precontracted with acetylcholine, with the rank or der of potency being Beraprost (1) greater-than-or-equal-to Iloprost ( 0.65) > PGI2 (0.04), accompanied by the corresponding increase in intr acellular cyclic AMP levels. The Beraprost- and PGI2-induced muscle re laxations were significantly inhibited by each of the PG antagonist di phloretin phosphate, the adenylate cyclase inhibitor SQ 22,536, and th e Na+-K+-ATPase inhibitor ouabain. Beraprost and PGI2 at concentration s insufficient to cause muscle relaxation reduced the contractile resp onses to electrical field stimulation, whereas they were without effec t on those to exogenous acetylcholine. These results suggest that Bera prost not only potently relaxes airway smooth muscle through cyclic AM P production and the subsequent stimulation of Na+-K+-ATPase but also reduces neurally mediated contraction by inhibiting the release of ace tylcholine from the cholinergic nerve terminals.